7-Oxabicycloheptane substituted oxamide prostaglandin analogs and their use in treating thrombolytic disease

Abstract

7-Oxabicycloheptane substituted oxamide prostaglandin analogs are provided having the structural formula ##STR1## and including all stereoisomers thereof. The compounds are cardiovascular agents useful, for example, in the treatment of thrombolytic disease.

What is claimed is: 
     
       1. A compound having the structural formula ##STR22## and including all stereoisomers thereof wherein A is --CH═CH-- or --(CH 2 ) 2  --; m is 1 to 8; n is 1 to 5;   R is hydrogen, lower alkyl or alkali metal;   R 1  and R 2  are the same or different and are selected from the group consisting of hydrogen, lower alkyl, aryl, aralkyl and cycloalkyl, wherein the term lower alkyl or alkyl by itself or as part of another group contains 1 to 12 carbons and is unsubstituted or substituted with halo, trifluoromethyl, alkoxy, aryl, alkyl-aryl, haloaryl, cycloalkyl or alkylcycloalkyl;   the term aryl by itself or as part of another group contains 6 to 10 carbons and is unsubstituted or substituted with lower alkyl, halogen or lower alkoxy;   the term cycloalkyl by itself or as part of another group contains 3 to 12 carbons and is unsubstituted or substituted with 1 or 2 halogens, 1 or 2 lower alkyl groups and/or 1 or 2 lower alkoxy groups, and the terms (CH 2 ) m  and (CH 2 ) n  may be unsubstituted or include one or more lower alkyl substituents.   
     
     
       2. THe compound as defined in claim 1 wherein R is H or CH 3 . 
     
     
       3. The compound as defined in claim 1 wherein A is --CH═CH--. 
     
     
       4. The compound as defined in claim 1 wherein A is --CH═CH--, m is 2 to 4, n is 1 to 3, R is H or CH 3 , R 1  is H and R 2  is lower alkyl or aryl. 
     
     
       5. The compound as defined in claim 1 wherein A is --CH═CH--, m is 3, n is 1, R is H, R 1  is H and R 2  is lower alkyl or phenyl. 
     
     
       6. The compound as defined in claim 1 having the name [1β,2α(5Z),3α,4β]-7-[3-[[[oxo(phenylamino)acetyl]amino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid or its methyl ester, and including all stereoisomers thereof. 
     
     
       7. A method of inhibiting arachidonic acid-induced platelet aggregation and bronchoconstriction, which comprises administering to the circulatory system of a mammalian host an effective amount of a compound as defined in claim 1 or a pharmaceutically acceptable salt thereof. 
     
     
       8. The method as defined in claim 7 wherein said compound is administered in an amount within the range of from about 1 to about 100 mg/kg. 
     
     
       9. A composition for inhibiting arachidonic acid-induced platelet aggregation and bronchoconstriction comprising an effective amount of a compound as defined in claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier therefor. 
     
     
       10. A method of inhibiting platelet aggregation which comprises administering to a mammalian host an effective amount of a compound as defined in claim 1 or a pharmaceutically acceptable salt thereof. 
     
     
       11. A method of inhibiting bronchoconstriction associated with asthma, which comprises administering to a mammalian host an effective amount of a compound as defined in claim 1 or a pharmaceutically acceptable salt thereof.